Lysophosphatidylserine induces necrosis in pressure overloaded male mouse hearts via G protein coupled receptor 34.

Heart failure is a leading cause of mortality in developed countries. Cell death is a key player in the development of heart failure. Calcium-independent phospholipase A2ß (iPLA2ß) produces lipid mediators by catalyzing lipids and induces nuclear shrinkage in caspase-independent cell death. Here, we show that lysophosphatidylserine generated by iPLA2ß induces necrotic cardiomyocyte death, as well as contractile dysfunction mediated through its receptor, G protein-coupled receptor 34 (GPR34). Cardiomyocyte-specific iPLA2ß-deficient male mice were subjected to pressure overload. While control mice showed left ventricular systolic dysfunction with necrotic cardiomyocyte death, iPLA2ß-deficient mice preserved cardiac function. Lipidomic analysis revealed a reduction of 18:0 lysophosphatidylserine in iPLA2ß-deficient hearts. Knockdown of Gpr34 attenuated 18:0 lysophosphatidylserine-induced necrosis in neonatal male rat cardiomyocytes, while the ablation of Gpr34 in male mice reduced the development of pressure overload-induced cardiac remodeling. Thus, the iPLA2ß-lysophosphatidylserine-GPR34-necrosis signaling axis plays a detrimental role in the heart in response to pressure overload.

Rubicon-regulated beta-1 adrenergic receptor recycling protects the heart from pressure overload.

Heart failure has high morbidity and mortality in the developed countries. Autophagy is important for the quality control of proteins and organelles in the heart. Rubicon (Run domain Beclin-1-interacting and cysteine-rich domain-containing protein) has been identified as a potent negative regulator of autophagy and endolysosomal trafficking. The aim of this study was to investigate the in vivo role of Rubicon-mediated autophagy and endosomal trafficking in the heart. We generated cardiomyocyte-specific Rubicon-deficient mice and subjected the mice to pressure overload by means of transverse aortic constriction. Rubicon-deficient mice showed heart failure with left ventricular dilatation, systolic dysfunction and lung congestion one week after pressure overload. While autophagic activity was unchanged, the protein amount of beta-1 adrenergic receptor was decreased in the pressure-overloaded Rubicon-deficient hearts. The increases in heart rate and systolic function by beta-1 adrenergic stimulation were significantly attenuated in pressure-overloaded Rubicon-deficient hearts. In isolated rat neonatal cardiomyocytes, the downregulation of the receptor by beta-1 adrenergic agonist was accelerated by knockdown of Rubicon through the inhibition of recycling of the receptor. Taken together, Rubicon protects the heart from pressure overload. Rubicon maintains the intracellular recycling of beta-1 adrenergic receptor, which might contribute to its cardioprotective effect.

Difference in left atrial D-dimer level in patients with atrial fibrillation treated with direct oral anticoagulant.

BACKGROUND: Atrial fibrillation (AF) may cause cerebral and systemic embolism. An increased D-dimer level indicates hyperactivation of secondary fibrinolysis, resulting in predilection for thrombosis. To clarify the differential effects of anticoagulation therapy, we compared the D-dimer levels in peripheral and left atrial (LA) blood of atrial fibrillation patients scheduled for ablation. METHODS: We analyzed 141 patients with non-valvular AF (dabigatran, n = 30; apixaban, n = 47; edoxaban, n = 64; mean age: 68 years, male: 60%). Peripheral venous blood and LA blood was collected before pulmonary vein isolation. We examined the laboratory and echocardiographic parameters. RESULTS: After adjusting for baseline characteristics, D-dimer level in the LA was significantly higher in patients treated with edoxaban than that in those on apixaban (0.77 ± 0.05 vs. 0.60 ± 0.05 µg/mL, P = 0.047), although there were no significant differences in peripheral D-dimer levels. We classified the D-dimer value of the LA into a normal group (< 0.9) and a high value group (≥ 1.0); the peripheral prothrombin fragment F1 + 2 level (odds ratio [OR] 1.012; 95% confidence interval [CI]: 1.003-1.022; P = 0.008) and left ventricular ejection fraction (LVEF) (OR, 0.947; 95% CI, 0.910-0.986; P = 0.008) were potential predictors of high LA D-dimer levels. CONCLUSIONS: In apixaban-treated patients, the D-dimer level in the left atrium was lower than in edoxaban-treated patients on the day of ablation, suggesting that the anticoagulant effect of apixaban on the left atrium is better than that of edoxaban in patients with AF.

Protracted impairment of left atrial compliance after cryoballoon ablation in recurrence-free patients with paroxysmal atrial fibrillation.

The relationship between alterations in left ventricular (LV) diastolic function and the incidence of recurrence, as well as the associated factors after cryoballoon (CB) and radiofrequency (RF) catheter ablation in patients with paroxysmal atrial fibrillation (Paf), require clarification. We enrolled 138 patients with Paf (RF/CB 69/69) who underwent the first catheter ablation and follow-up for 12 months. Transthoracic echocardiography was performed before and after ablation. An afterload-integrated index of LV diastolic function was calculated as diastolic elastance (Ed)/arterial elastance (Ea), Ed/Ea. No significant increases were observed in Ed/Ea 3 days after RF ablation in patients with (n=12) and without (n=57) recurrence. However, a significant increase was observed in recurrence-free patients with CB ablation (n=59; P<0.05), although this level was restored after 6 months. Ed/Ea 3 days after CB ablation was correlated with left atrial pressure immediately after (r=0.630, P<0.001), but not before (r=0.290, P=0.159), ablation. The increment of creatine kinase- myocardial band release was positively associated with that of Ed/Ea (r=0.388, P<0.05) after CB ablation. Thus, the transient manifestation of LV diastolic dysfunction after CB ablation, evaluated by a new echocardiographic index, was observed only in recurrence-free patients with Paf. Protracted impairment of left atrial compliance due to ablation-induced myocardial injury may be related to the lack of recurrence in patients after CB ablation.

Short-duration, submaximal intensity exercise stress combined with adenosine triphosphate decreases artifacts in myocardial perfusion single-photon emission computed tomography.

BACKGROUND: Myocardial perfusion single-photon emission computed tomography (SPECT) imaging with stress is a useful examination for detecting coronary artery disease. Since the presence of artifacts is remaining challenges, we aimed to define the minimum intensity of low-grade exercise stress levels combined with drug stress to reduce undesired artifacts and their related factors. METHODS: We divided patients with suspicious coronary artery disease into 4 groups as follows: group A, adenosine triphosphate (ATP) for 6 min; group A + 25 W, ATP + 25 W exercise for 6 min; group A + 35 W, ATP + 35 W exercise for 6 min; group A + 45 W, ATP + 45 W exercise for 6 min) and enrolled only those whose summed stress scores were < 3. Undesired artifacts were evaluated on the basis of heart-to-liver activity (H/L) ratio and heart-to-10 pixels below the heart (H/below the H) ratio. RESULTS: The logarithmic values of H/L and H/below the H ratios were significantly higher in groups A + 35 W and A + 45 W than in group A (p < 0.05, each). In all the patients, the logarithmic values of H/L and H/below the H ratios positively correlated with the increment of rate pressure product (RPP, p = 0.002 and p = 0.005, respectively) after stress in the univariate analysis. The left ventricular end-diastolic volume (LVEDV) after stress (p = 0.002) negatively correlated with the logarithmic value of H/below the H ratio, but not H/L ratio. Although the increment of RPP was independently associated with the logarithmic values of both H/L (p = 0.001) and H/below the H ratios (p = 0.005), LVEDV was also independently associated with the logarithmic value of H/below the H ratio (p < 0.001) in multivariate regression analysis under adjusting with age and sex. CONCLUSION: ATP plus ≥35 W exercise stress for 6 min was useful for reducing undesired artifacts after stress in myocardial perfusion SPECT. LVEDV after stress in addition to the increment of RPP was independently associated with the H/below the H ratio, but not the H/L ratio.

Tolvaptan-induced hypernatremia related to low serum potassium level accompanying high blood pressure in patients with acute decompensated heart failure.

BACKGROUNDS: Tolvaptan significantly increases urine volume in acute decompensated heart failure (ADHF); serum sodium level increases due to aquaresis in almost all cases. We aimed to elucidate clinical factors associated with hypernatremia in ADHF patients treated with tolvaptan. METHODS: We enrolled 117 ADHF patients treated with tolvaptan in addition to standard therapy. We examined differences in clinical factors at baseline between patients with and without hypernatremia in the initial three days of hospitalization. RESULTS: Systolic (p = 0.045) and diastolic (p = 0.004) blood pressure, serum sodium level (p = 0.002), and negative water balance (p = 0.036) were significantly higher and serum potassium level (p = 0.026) was significantly lower on admission day in patients with hypernatremia (n = 22). In multivariate regression analysis, hypernatremia was associated with low serum potassium level (p = 0.034). Among patients with serum potassium level ≤ 3.8 mEq/L, the cutoff value obtained using receiver operating characteristic curve analysis, those with hypernatremia related to tolvaptan treatment showed significantly higher diastolic blood pressure on admission day (p = 0.004). CONCLUSION: In tolvaptan treatment combined with standard therapy in ADHF patients, serum potassium level ≤ 3.8 mEq/L may be a determinant factor for hypernatremia development. Among hypokalemic patients, those with higher diastolic blood pressure on admission may be carefully managed to prevent hypernatremia.

Pressure- and Velocity-Based Physiological Assessment of Stenotic Lesions at Hyperemia in Superficial Femoral Artery Disease: Importance of Hyperemic Stenosis Resistance.

Background: In superficial femoral artery (SFA) stenosis, stenosis resistance may increase, but the relationship between stenosis resistance and stenotic severity remains to be seen. This study aimed to investigate the physiological response, through a hyperemic condition, and the pathophysiological significance of Doppler flow and stenosis resistance in SFA. Methods: Twenty-four limbs with focal stenosis of the SFA were analyzed. We assessed the fractional flow reserve (FFR), hyperemic stenosis resistance (h-SR), and vascular flow reserve (VFR) of the SFA with a pressure/Doppler flow sensor-tipped combination guidewire before and after endovascular therapy (EVT). Results: FFR, h-SR, and VFR changed significantly after EVT. h-SR was more strongly correlated with % area stenosis, measured by intravascular ultrasound than FFR (FFR: r=-0.716, h-SR: r=0.741, p<0.0001, respectively). However, VFR was not associated with % area stenosis. A receiver operating characteristic curve showed cut-offs h-SR >0.36 mmHg·sec/cm, and FFR <0.88 predicted >75% area stenosis with area under curves of 0.883 and 0.828, respectively. Conclusion: h-SR can indicate stenotic severity in an SFA focal lesion more prominently than FFR and may be a new physiological index to determine indication for EVT. VFR was not feasible for assessment in SFA focal stenosis.

Inferior Vena Cava Occlusion and Ilio-Iliac Arteriovenous Fistula Caused by Tumor Invasion: A Case Report.

An 80-year-old woman presented with general fatigue and leg edema for several months. Ultrasonography and contrast-enhanced computed tomographic angiography revealed inferior vena cava thrombosis, ilio-iliac arteriovenous fistula (AVF), and iliac artery pseudoaneurysm. Furthermore, malignant cells were observed in the aspirated thrombus. Although thrombus aspiration and anticoagulant therapy were unsuccessful in reducing the thrombotic mass and alleviating her symptoms, endovascular therapy for AVF and pseudoaneurysm improved her leg edema without recurrence or any endoleak. These findings highlight that endovascular therapy can be effective in older adults with cancer because of its low invasiveness.

Transient manifestation of left ventricular diastolic dysfunction following ablation in patients with paroxysmal atrial fibrillation.

BACKGROUND: In patients with atrial fibrillation, ablation decreases left atrial (LA) compliance, which may lead to left ventricular (LV) diastolic dysfunction. We aimed to examine serial changes in LV diastolic function after 2 ablation procedures and their related factors in patients with paroxysmal atrial fibrillation (PAF). HYPOTHESIS: LV diastolic function is different after 2 ablation procedures. METHODS: We enrolled 132 patients with PAF (76 males, mean age 67 years; cryoballoon [CB] ablation/radiofrequency [RF] ablation 60/72) who underwent a single ablation procedure. The transthoracic echocardiographic parameters were obtained before, 3 days after, and 6 months after ablation. RESULTS: The afterload-related index of LV diastolic function, Ed/Ea = E/e' / (0.9 × systolic blood pressure), increased significantly at 3 days after ablation, especially after CB ablation (P <0.05), although no differences were observed in age, sex, LA size, LV size, and E/e' before ablation between CB ablation and RF ablation. Creatine kinase release after ablation was significantly higher in CB ablation than in RF ablation (P <0.001). The increment of Ed/Ea after CB ablation was positively correlated with LV ejection fraction (LVEF) before ablation (r =0.416; P <0.05). The elderly (age ≥ 75 years), females, and patients with hypertension were more likely to show impaired LV diastolic function transiently after 3 days of ablation, but the diastolic index was restored to baseline level after 6 months. CONCLUSIONS: The increased Ed/Ea after CB ablation represented transient manifestation of underlying LV diastolic dysfunction in PAF patients with preserved LVEF with older age, female sex, and a history of hypertension.

A case of successful bystander cardiopulmonary resuscitation of an adult with Bland-White-Garland syndrome.

In Japan and worldwide, the increase in educational interventions about resuscitation training significantly increases favorable neurological survival in out-of-hospital cardiopulmonary arrest cases treated with bystander cardiopulmonary resuscitation (BCPR) each year. This case with Bland-White-Garland syndrome having high-quality BCPR by nurses demonstrates the importance of education about BCPR.